A SNARE geranylgeranyltransferase essential for the organization of the Golgi apparatus

EMBO J. 2020 Apr 15;39(8):e104120. doi: 10.15252/embj.2019104120. Epub 2020 Mar 3.

Abstract

Protein prenylation is essential for many cellular processes including signal transduction, cytoskeletal reorganization, and membrane trafficking. Here, we identify a novel type of protein prenyltransferase, which we named geranylgeranyltransferase type-III (GGTase-III). GGTase-III consists of prenyltransferase alpha subunit repeat containing 1 (PTAR1) and the β subunit of RabGGTase. Using a biotinylated geranylgeranyl analogue, we identified the Golgi SNARE protein Ykt6 as a substrate of GGTase-III. GGTase-III transfers a geranylgeranyl group to mono-farnesylated Ykt6, generating doubly prenylated Ykt6. The crystal structure of GGTase-III in complex with Ykt6 provides structural basis for Ykt6 double prenylation. In GGTase-III-deficient cells, Ykt6 remained in a singly prenylated form, and the Golgi SNARE complex assembly was severely impaired. Consequently, the Golgi apparatus was structurally disorganized, and intra-Golgi protein trafficking was delayed. Our findings reveal a fourth type of protein prenyltransferase that generates geranylgeranyl-farnesyl Ykt6. Double prenylation of Ykt6 is essential for the structural and functional organization of the Golgi apparatus.

Keywords: SNARE; Golgi; PTAR1; Ykt6; protein prenylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkyl and Aryl Transferases / chemistry
  • Alkyl and Aryl Transferases / genetics
  • Alkyl and Aryl Transferases / metabolism*
  • Animals
  • Dimethylallyltranstransferase / chemistry
  • Dimethylallyltranstransferase / genetics
  • Dimethylallyltranstransferase / metabolism*
  • Golgi Apparatus / metabolism
  • Humans
  • Male
  • Membrane Fusion
  • Protein Binding
  • Protein Multimerization
  • Protein Prenylation
  • Protein Transport
  • R-SNARE Proteins / genetics
  • R-SNARE Proteins / metabolism*
  • Rats
  • Rats, Wistar
  • SNARE Proteins / metabolism*

Substances

  • R-SNARE Proteins
  • SNARE Proteins
  • YKT6 protein, human
  • Alkyl and Aryl Transferases
  • RABGGTB protein, human
  • Dimethylallyltranstransferase
  • PTAR1 protein, human

Associated data

  • PDB/6J6X
  • PDB/6J74
  • PDB/6J7X
  • PDB/6J7F